Oxidative acetylation of tetramethyl bisphenol-F

Article abstract of DOI:10.1080/00397910500408928

Oxidative acetylation of tetramethyl bisphenol-F (2) using two different reagents is described. The reaction of (2) with NaIO₄ in acetic anhydride furnished a novel triacetate (3) and its reaction with lead tetraacetate (LTA) in dry benzene resulted in the formation of a novel bis-cyclohexadienone (4). Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500408928

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Synthetic Communications , 36: 673–678, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500408928
Oxidative Acetylation of Tetramethyl
Bisphenol-F
Pradeep T. Deota and Hemant S. Parmar
Applied Chemistry Department, Faculty of Technology and Engineering,
Maharaja Sayajirao University of Baroda, Vadodara, India
Vaibhav B. Valodkar and Piyush R. Upadhyay
Department of Chemistry, Faculty of Science, Maharaja Sayajirao
University of Baroda, Vadodara, India
S. P. Sahoo
Sun Pharmaceutical Advance Research Centre, Vadodara, India
Abstract: Oxidative acetylation of tetramethyl bisphenol-F (2) using two different
4
reagents is described. The reaction of (2) with NaIO in acetic anhydride furnished a
novel triacetate (3) and its reaction with lead tetraacetate (LTA) in dry benzene
resulted in the formation of a novel bis-cyclohexadienone (4).
Keywords: Bis(3,5-dimethyl-4-hydroxyphenyl)methane, bis(3,5-dimethyl-3-acetoxy-
4-oxocyclohexa-1,5-dienyl)methane, cyclohexa-2,4-dienones, oxidative acetylation
Cyclohexa-2,4-dienones are useful intermediates for preparing a variety of
1–4]
[
complex natural products.
synthesis of acetoxy-2,4-cyclohexadienones by treatment of substituted
We have recently reported a one-pot
[5]
phenols with sodium metaperiodate in acetic anhydride. Our continued
efforts in this area prompted us to synthesize tetramethyl bisphenol-F (2)
6]
and investigate its reaction with LTA as well as with sodium metaperiodate
[
[
5]
in acetic anhydride.
Received in India August 22, 2005
Address correspondence to Pradeep T. Deota, Applied Chemistry Department,
Faculty of Technology and Engineering, Maharaja Sayajirao University of Baroda,
Vadodara 390 001, India. E-mail: deotapt@yahoo.com
6
73

6
74
P. T. Deota et al.
The bisphenol-F (2) was prepared from 2,6-dimethylphenol (1) by
modifying the procedure of Kharasch et al. reported for the preparation of
0 0 0
[7]
,3 ,5,5 -tetra-tert-butyl-4,4 -dihydroxy diphenyl methane. Thus, treatment
3
of 2,6-dimethylphenol (1) with formaldehyde solution (37% w/v) in
the presence of aqueous sodium hydroxide at 858C for 5 h resulted in the
formation of tetramethyl bisphenol-F (2) in 52% yield (Scheme 1) The
structure of (2) was readily established through its spectral and analytical
1
data. Its H NMR spectra exhibited a singlet at d 3.7 for two protons and a
H
broad singlet at 2.2 for twelve protons on methyl groups along with a
singlet at 4.5 for two exchangeable protons, indicating the presence of two
1
3
phenolic OH groups. The C NMR of (2) displayed diagnostic signals at
dC 16.49 for four methyl carbons and a signal at 40.16 for the methylene
carbon, among other characteristic signals for aromatic carbons. Its mass
spectrum was also consistent with the structure that showed the molecular
ion peak at 258 and a base peak at 135 (M-121).
Treatment of (2) with sodium metaperiodate in acetic anhydride at
5–808C for 5 h resulted in the formation of a novel triacetate (3) whose
7
Scheme 1.

Oxidative Acetylation of Tetramethyl Bisphenol-F
675
structure was fully established through its spectral and analytical data. It
2
showed a characteristic band at 1749 cm for the carbonyl absorption in its
1
IR spectrum. It also displayed singlets for methyl groups at d 2.14 (12H)
H
1
along with 2.15 (3H) and 2.26 (6H). Its C NMR spectrum showed signals
3
at d 170.1 and 168.9 for acetate carbonyls along with 21.6 and 20.7 for
C
acetate methyls. The mass spectrum of (3) showed a molecular ion peak at
3
98 and a base peak at 339 (loss of acetic acid) in addition to other diagnostic
signals. It was evident that acetylation of the two phenolic OH groups and at
the benzylic position led to the formation of the triacetate (3).
The compound (2) was then treated with LTA in dry benzene for 1 h at
room temperature (ꢀ278C). Usual workup and chromatography over silica
gel furnished the novel bis(3,5-dimethyl-3-acetoxy-4-oxocyclohexa-1,5-
dienyl)methane (4) in 45% yield. The structure of the compound (4) was
confirmed through its spectral and analytical characteristics. The bis-
2
1
cyclohexadienone (4) showed a characteristic band at 1669 cm in its IR
[
spectrum for cyclohexadienones. Its H NMR spectrum displayed signals
8]
1
at d 1.37, 1.92, and 2.06 each for 6H along with singlets at 3.05 (2H) and
H
1
.86 (2H) for methylene and olefinic protons respectively. The C NMR
3
5
spectrum of (4) was also consistent with the proposed structure and
exhibited resonances at d 15.90, 21.07, and 24.63 for methyl carbons and a
C
signal at 40.51 for the methylene carbon in addition to other characteristic
signals. Its mass spectrum showed a molecular ion peak at 372 and a base
peak at 313 (M-59) indicating loss of acetate ion and was correctly
analyzed for C H O . It was interesting to observe that both the aromatic
2
1 24 6
rings participated in the oxidation leading to the novel bis-cyclohexadienone
4). It is also noteworthy that although the oxidative acetylation of tetramethyl
(
bisphenol-F could lead in principle to the formation of several addition
products through inter- and intramolecular modes of cycloaddition, the
reaction only furnished a single product (4). To study its possible intra- as
well as intermolecular cycloaddition reactions, the bis-dienone (4) was also
heated under reflux in o-xylene for 5 h with stirring. We observed that the
bis-dienone (4) is stable under the reaction conditions and remained
[
9]
unchanged. It is also worthwhile to mention here that the tetramethyl
bisphenol-F (2) was found to be stable toward oxidation with NaIO in
4
[9,10]
water even at 808C and did not yield any cyclohexadienone.
Further investigation on the reactivities of the novel acetates (3) and (4) is
currently under way.
EXPERIMENTAL
IR spectra were recorded on a Perkin–Elmer PC-16 FTIR spectrophotometer.
NMR spectra were recorded on either a Bruker-200 FT-NMR or Bruker-300
FT-NMR spectrophotometer. Mass spectra were obtained on a Shimadzu
QP-5050A mass spectrophotometer with quadrupole detector. Microanalyses

6
76
P. T. Deota et al.
were performed on a Perkin–Elmer 2400 CHN/S Analyzer instrument.
Column chromatography was performed using Acme’s silica gel (60–120
mesh size) and spots on TLC were visualized in iodine vapor.
Tetramethyl Bisphenol-F [Bis(3,5-dimethyl-4-
hydroxyphenyl)methane] (2)
An aqueous solution of sodium hydroxide (22 mL, 23% w/v, 0.126 mol) was
added to a stirred mixture of 2,6-dimethyl phenol (1) (10.0 gm, 0.082 mol) in
ethyl alcohol (30 mL) and formaldehyde (15 mL, 37% w/v, 0.185 mol) over a
period of 15min. The reaction mixture was heated at 85–908C for 5 h under
continuous stirring. The reaction mixture was then allowed to cool down to
room temperature and was diluted ten times its volume with water and stirred
for 15min. The solid thus obtained was filtered and washed thoroughly with
water and dried at 85–908C under vacuum. The solid mass thus obtained was
dissolved in ethyl acetate (100mL), and the solution was dried over anhydrous
sodium sulphate. Column chromatography of the residue over silica gel and
elution (light petroleum/ethyl acetate, 95: 5) furnished (2) as a white crystalline
solid (52%). Mp 180–1828C, nmax (neat) 3463, 3007, 2915, 2847, 1629, 1608,
21
1484, 1304, 1227, 1186, 1145, 1013, 882, 774, 730, and 5765cm . d (200
MHZ, CDCl ); 2.2 (s, 12H, methyl), 3.7 (s, 2H, methylenes), 4.5 (s, 2H,
H
3
exchangeable, phenolic OH), 6.8 (s, 4H, aromatic H). d (50 MHZ, CDCl ):
C
3
þ
1
6.49, 40.16, 124.02, 128.37, 132.62, 151.02. M/z: 256 (M ), 135 (M-121)
base peak: loss of 2,6-dimethyl phenol). Elemental analysis found: C,
9.80%; H, 7.94%; requires C, 79.69%; H, 7.81% for C H O .
(
7
1
7 20 2
Bis(4-acetoxy-3,5-dimethylphenyl)methyl Acetate (3)
Sodium metaperiodate (1.5 gm, 0.007 mol, excess) was added to a stirred
solution of bis(3,5-dimethyl-4-hydroxyphenyl)methane (2) (0.50 gm, 0.00195
mol) in acetic anhydride (15 mL) in portions over a period of 1 h. Stirring was
continued for 5 h while maintaining the reaction temperature between 75 and
808C. The reaction mixture was allowed to cool down to room temperature
and then poured into a vigorously stirred saturated solution of sodium bicarbon-
ate (125 mL) to neutralize excess acid. The aqueous layer was then extracted
with ethyl acetate (3 ꢀ 25 mL) and combined organic extracts were succes-
sively washed with saturated sodium bicarbonate solution (20 mL), water
(20 mL), and brine solution (20 mL). Drying over anhydrous sodium sulphate
followed by removal of solvent under reduced pressure furnished a dark
brown residue, which was chromatographed using a mixture of light
petroleum and ethyl acetate (95 : 5) to furnish the acetylated product (3) as a
white crystalline solid (0.414 gm, 51.28%). Mp 1398C, (lmax): 250 nm; nmax
2
1
(
neat) 3469, 3016, 2929, 1749, 1607, 1370, 1144 cm . dH (300 MHZ,

Oxidative Acetylation of Tetramethyl Bisphenol-F
CDCl ); 2.14 (sharp s, 12H, –CH on aromatic rings), 2.15 (s, 3H, –OCOCH
3
677
3
3
on the central tetra-substituted carbon), 2.26 (sharp s, 6H, acetate methyl
protons), 6.75 (s, 1H, methane proton), 7.02 (s, 4H, aromatic Hs). dC (75
MHZ, CDCl ): 170.1, 168.9, 148.0, 137.6, 130.5, 127.5, 76.1, 21.6, 20.7,
3
þ
1
CH CO), 255 (loss of another CH CO). Elemental analysis found: C,
6.6. M/z: 398 (M ), 339 (base peak, M-60, loss of acetic acid), 297 (loss of
3
3
6
8.93%; H, 6.43%; requires C, 69.34%; H, 6.53% for C H O .
23 26 6
Bis(3,5-dimethyl-3-acetoxy-4-oxocyclohexa-1,5-dienyl)methane (4)
LTA (2.66 gm, 0.006 mol) was added to a solution of bis(3,5-dimethyl-4-
hydroxyphenyl)methane (2) (0.5gm, 0.002 mol) in dry benzene (30 mL) in
portions with constant stirring. The reaction mixture was stirred for 1 h at room
temperature (ꢀ278C) after which it was diluted with ethyl acetate (150mL)
and stirred further for 15min. Removal of the residue by filtration and concen-
tration of the filtrate furnished a pale yellow liquid, which was chromatographed
over a column of silica gel. Elution of the column (light petroleum/ethyl acetate
9
5: 5) gave (4) as a light yellow crystalline solid (45%). Mp 183–1848C, nmax
neat): 2994, 2919, 1734, 1669, 1437, 1371, 1253, 1225, 1060, 859, and
(
21
762 cm . d (200 MHZ, CDCl ); 1.37 (s, 6H, methyl protons), 1.92 (s, 6H,
H 3
olefinic methyl protons), 2.06 (s, 6H, acetate methyl protons), 3.05 (s, 2H,
methylene protons), 5.86 (s, 2H, olefinic H), 6.59 (s, 2H, olefinic H). d (50
C
MHZ, CDCl ): 15.90, 21.07, 24.63, 40.51, 78.93, 131.26, 134.61, 137.03,
3
þ
1
base peak), (M-119) (loss of two acetate ions). Elemental analysis found: C,
39.85, 169.91, 199.31. M/z: 372.0 (M ), 313 (M-59) (loss of acetate ion,
6
7.71%; H, 6.44%; requires C, 67.74%; H, 6.45% for C H O .
21 24 6
ACKNOWLEDGMENTS
We thank Madhusudanan (CDRI), Lucknow, India, for his help in providing
spectral analysis.
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1